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Study to determine Alzheimer’s theory

magnifying glass on a picture of somebody's brain
magnifying glass on a picture of somebody's brain Image credit: mcgill.ca

It’s still not known what causes Alzheimers, but for years scientists believe a sticky substance called beta-amyloid is behind why 1 in 3 of us will go on to develop dementia.

To test out the theory once and for all a new study will see a group of volunteers, aged 18 and over, take a course of anti-amyloid drugs to determine if the professionals are correct.

Over the years a number of experimental drugs have failed to stop a decline in the loss of memory and thinking, despite eradicating amyloid from people with early stages of Alzheimer’s.

"Many of us think of that as the ultimate test of the amyloid hypothesis," says Dr. Randall Bateman, a professor of neurology at Washington University School of Medicine in St. Louis, told NPR. "If that doesn't work, nothing will work." 

The DIAN-TU primary Prevention Trial, is due to be rolled out later this year.

It was Dr. Alois Alzheimer who first came up with the theory behind the condition which was attached to his name after he first described the symptoms in 1906.

The pathologist conducted an autopsy on a woman who died from memory loss, disorientation and hallucinations; he found an "unusual disease of the cerebral cortex," including "senile plaque" commonly seen in older people.

In 1980 further research showed the plaques were formed of beta-amyloid, a substance found in the brain.

"We have 30 years of solid data, thousands of studies that all say this is sufficient to cause Alzheimer's," Bateman said.

For years scientists have been trying to prove amyloid is linked to Alzheimer’s, but the studies have been unsuccessful.

"Penicillin, a great breakthrough, failed its first two clinical trials," Bateman said. "Fortunately, people didn't say, oh, the antibiotic theory is a bad idea and we should give up on it."

Some studies were more successful than others, for example the Gantenerumab drug delayed a number of brain changes linked with the death of brain cells.

And then there was the study into experimental drug lecanemab which slowed down loss of memory and thinking in a study of 1,800 people living with Alzhiemer’s.

Some studies may not have had success rates because they were trailed on people who already had amyloid plaques in their brains.

"My prediction is it will work, and it will work fantastically," Bateman told the publication. "If we can really prevent the plaques from starting and taking off and those downstream changes from going, my prediction is that those people will never get Alzheimer's."

Dr. Eric McDade, a professor of neurology at Washington University, is overseeing the new experiment.

"What we're trying to do is to prevent that amyloid pathology from developing in the first place," McDade said.

"At the point of somebody having symptoms, we know now that they probably have had amyloid in their brain for one to two decades.”

The four-year-study will see around 160 volunteers with dominantly inherited Alzheimer’s disease, caused by rare, inherited gene mutations that go on to develop the condition in middle age.

"The earliest they can come in is 25 years before we anticipate they would start to develop symptoms," McDade said. "For most of these families, that actually puts them in their mid 20s when we're going to start this trial."

The study will see volunteers prescribed the anti-amyloid drug gantenerumab which was used in the previous unsuccessful trial.

If amyloid plaques do not develop the study will then go on to identify if the drug prevents the appearance of other markers of Alzheimer’s effects on the brain, such as brain atrophy which causes shrinkage in one or more areas of the cerebrum.

"If we prevent amyloid pathology from developing and these other markers continue to develop and unfold," McDade concluded, "this would be one of the best ways to say, listen, amyloid is really not what we should be targeting."

For more information and advice on Alzheimer’s visit the Alzheimer’s Society website.